Author/Authors :
Mark T. Goulet، نويسنده , , Shelli R. McAlpine، نويسنده , , Mary Jo Staruch، نويسنده , , Samuel Koprak، نويسنده , , Francis J. Dumont، نويسنده , , John G. Cryan، نويسنده , , Gregory J. Wiederrecht، نويسنده , , Raymond Rosa، نويسنده , , Mary Beth Wilusz، نويسنده , , Laurence B. Peterson، نويسنده , , Matthew J. Wyvratt Jr.، نويسنده , , William H. Parsons، نويسنده ,
Abstract :
A series of C32-O-aralkyl ether derivatives of the FK-506 related macrolide ascomycin have been prepared based on an earlier reported C32-O-cinnamyl ether design. In the present study, the nature of the aryl tethering group was varied in an attempt to improve oral activity. An imidazol-2-yl-methyl tether was found to be superior among those investigated and has resulted in an ascomycin analog, L-733,725, with in vivo immunosuppressive activity comparable to FK-506 but with an improved therapeutic index.
